[c-Ski improves beagle atrial structural remodeling by suppressing TGF-β1-SMAD signaling and p38 MAPK pathway]

Objective To investigate the role and mechanism of c-Ski in atrial structural remodeling by rapid atrial pacing in a canine model. Methods The expression levels of c-Ski, α-smooth muscle actin (α-SMA) and type III collagen (Col3) in atrial tissues of patients with atrial fibrillation (AF) and their correlations were detected by real time quantitative PCR and Pearson's correlation analysis. A canine atrial rapid pacing model was constructed. The expression and distribution of α-SMA and Col3 were detected by immunohistochemical staining. The levels of inflammatory cytokines interleukin-18 (IL-18) and Toll-like receptor 4 (TLR4) in serum and atrial tissues were determined by ELISA. The regulation effect of c-Ski on α-SMA, Col3, transforming growth factor β1 (TGF-β1)/SMAD pathway and p38 MAPK pathway were overexpressed and detected by Western blotting. Results c-Ski expression was down-regulated in the atrial tissues of AF patients, and showed a negative correlation with the expression of α-SMA and Col3 in AF. In addition, c-Ski expression showed a down-regulation in the canine atrial rapid pacing model. Overexpression of c-Ski significantly inhibited α-SMA and Col3 levels, as well as levels of inflammatory cytokines IL-18 and TLR4 in serum and atrial tissues, and alleviated AF induced atrial fibrosis by inhibiting TGF-β1-Smad pathway and p38 MAPK pathway in the canine atrial rapid pacing model. Conclusion Overexpression of c-Ski can improve atrial structural remodeling induced by rapid pacing by inhibiting TGF-β1-SMAD pathway and p38 MAPK pathway.